Device for automatic analysis of a liquid sample

ABSTRACT

The invention relates to a device comprising a series of single-use cuvettes (C), each with a base, an upper face opposite said base with an opening and two opposing flanges (R&lt;sb&gt;1&lt;/sb&gt;, R&lt;sb&gt;2&lt;/sb&gt;) which each extend from the cuvette essentially in the plane of the opening. Said cuvettes are arranged side by side and fixed to each other by means of a flexible film ( 3 ) fixed to said flanges (R&lt;sb&gt;1&lt;/sb&gt;, R&lt;sb&gt;2&lt;/sb&gt;) and at least partially covering the openings of said cuvettes (C). Said film is provided with a series of openings ( 4 ) respectively arranged to the right of said openings on said cuvettes. The above finds application in an automatic analytical apparatus, particularly for the determination of the rate of change of the physical state of a medium.

The present invention concerns a device for automatically analysing aliquid sample. It is more specifically but not exclusively aimed atimproving an automatic device able to be used for determining themodification times of a medium in a physical state.

This device is particularly applicable to determining blood coagulationin accordance with a process according to which the blood sample isplaced at the bottom of a bowl containing a ferromagnetic ball driven ina periodic movement under the effect of an external magnetic field. Themodifications of the movements of the ferromagnetic ball (for examplethe amplitude and/or frequency variations), which are representative ofchanges of the physical state of the blood, are then detected with theaid of suitable means.

This type of device is described in the patent WO 99 64839 filed in thename of the Junior Instruments company.

It includes a bowl distributor for sole usage, each bowl comprising abent inward bottom constituting the rolling path of the ball, and a faceopposite the bottom having an opening. These bowls are placed side byside and fixed on a flexible film in such a way that they can be moved,said film sealing off their openings. The film equipped with bowls canbe wound onto a coil able to be engaged on an element provided in astorage and distribution compartment of the device. The bowls run offone by one into a detection station.

As the support film seals off the openings of the bowl, a slit needs tobe made by incision so as to allow the pipette to pass through. Oncethis is done, pressure is exerted on the film so as to disconnect thebowl.

Moreover, the presence of this slit renders the pipette operation moredelicate with a risk of staining the film.

In addition, the presence of the film implies the use of a powerfullight source and the homogeneity of the beam generated by this sourcethrough the bowl shall be disturbed by both the presence of the slit andany possible stains present on the film. Moreover, the heterogeneousmedium traversed by the beam generated by the source generates multiplereflections, especially against the walls and edges of the bowls, whichrisks falsifying the analysis of the movement of the ferromagnetic ball.

Therefore, the object of the invention is to resolve these drawbacks.

To this effect, it concerns a device for the automated analysis of aliquid sample, said device comprising a series of bowls for sole usage,each comprising a bottom, one upper face opposite the bottom having oneopening and two opposing shoulders extending on both sides of the bowlapproximately inside the plane of the opening, the bowls being placedside by side and joined to each other by a flexible film secured to saidshoulders and covering, at least partially, the openings of said bowls.According to the invention, this device is characterised in that thefilm has a series of orifices situated respectively at the right of theopenings of the bowls.

The device may comprise an optical detection station introducing a lightsource, for example infrared, illuminating the upper face of the bowland an opto-electronic detector placed below the bottom, the aim of thelight being intended to allow reading of the movement of the ball viaopto-electronic detection.

In this case, the film can be made from a diffusing material for theinfrared light rendering the lighting luminous beam more homogeneous.The dimensions of the orifice shall then be determined in particularaccording to the dimensions of the pipette, its position and thesought-after homogeneity of the intensity of the luminous beamstraversing a predetermined effective volume of the bowl.

In a case where the device determines the modification times of thephysical state of a sample contained in the bowl by detecting themovements of a ball moving on the bottom of the bowl, said orifice couldhave the shape of an oblong opening centered partially on the rollingpath of the ball and whose width is slightly smaller than the diameterof the ball.

Advantageously, the material constituting the film could have liquidabsorption properties, such as pores, so as to fix any possibleprojections of liquid and of therefore reducing the risks ofcontamination of the samples contained in the bowls adjacent to the bowlcurrently being analysed.

This device could also comprise a pipette station introducing a pipettemoving transversally with respect to the reeling off axis of the bowls.So as to mitigate an inaccuracy of the movement of the pipette, applyingsaid pipette to the film or its edges possibly resulting in the fallingout of step unhooking of the bowls and/or the projections, the orificesof the film extending along an axis transversal to said reeling off axisof the bowls.

Moreover, this device could comprise a station for cutting the analysedbowls so as to receive them in a single container.

It is to be noted that this bowls/film unit remains adaptable to alreadyexisting models.

One embodiment of the invention is described hereafter and is given byway of non-restrictive example with reference to the accompanyingdrawings on which:

FIG. 1 is a diagrammatic representation of an average-sized automaticanalysis device;

FIG. 2 is a diagrammatic perspective view of a bowl mounted on the film;

FIG. 3 is a diagrammatic top view of the film equipped with its bowlsand the rack drive system;

FIG. 4 is a diagrammatic vertical section along A/A of FIG. 3.

In this example, the automatic analysis device 1 introduces a bowl feedcomprising a series of about one hundred bowls forming a strip 2.

As shown on FIG. 2, the bowls C embodied by moulding a transparentplastic material, each bowl having a flat parallelpiped-shaped bodywhose bent inward bottom FI constitutes a rolling path for aferromagnetic ball BE. Opposite this bottom FI, the bowl C has anopening, its two opposing edges BO₁, BO₂ being extended at a right angleby two respective shoulders R₁, R₂ each provided with a cylindricalprotuberance PC extending on the side opposite the body. These twoprotuberances are intended to be forcefully engaged in two respectiveholes TR respectively provided on the two lateral borders of the film.The shoulders R₁, R₂ have for example the shape of an isoscelestrapezium whose large base is integral with the bowl. The lateralborders of a support film 3 then have in the interval of the shouldersR₁, R₂ of the bowls sets of trapezoidal cuts whose oblique edges extendto the right of the oblique edges of the shoulders R₁, R₂ of the bowls.Thanks to these provisions, the side edges of film present each one anotched profile whose teeth are accentuated by the edges R1, R2 of thebowls.

The film is flexible and is made of an absorbent material, such aspaper. Each bowl is pierced at the top with an oblong orifice 4extending along the longitudinal axis of the bowls transversally to therun-off axis of the bowls.

According to the device shown on FIG. 4, the strip of bowls 2 is guidedby a rail 5. This rail has a U-shaped section whose two vertical wingsare extended at a right angle by two shoulders R₃, R₄, the shoulders R1,R2 rest onto the shoulders R3, R4. The strip passes in successionthrough a pipette station 6, a detection station 7 and a cutting station8 at the outlet of which each analysed bowl being recovered in acontainer 9 provided for this purpose.

The functioning of these various stations is controlled by a processor Pcomprising a central unit and peripheral units, such as a screen10/keyboard 11 unit.

The driving of the film 3 is ensured by a drive mechanism introducing anendless belt 12 guided at each extremity by rollers 13, 14. This beltcomprises a serration whose notches are spaced by a distance equal to amultiple of the width of the bowls (for example 4-5 bowls). Thesenotches have an involute to a circle profile which corresponds to anormal tooth-shaped rack so as to fully gear between the teeth of theserrated profile of the strip; thus, these notches accurately drive thestrip of bowls with self-centering and compensation of any possibleplay.

The pipette station 6 is controlled by an automated verticalheight-adjustable pipette 15 so as to be able to assume a lower pipetteor rinsing position and an upper position enabling it to move inside ahorizontal plane.

This pipette 15 is fixed to one of the extremities of an arm 16 mountedrotating by its other extremity around a vertical spindle 17. Thedriving in rotation of the arm 16 is ensured by a motor controlled bythe processor P.

By means of this particularly simple mechanism, the pipette 15 can besuccessively brought to the pipette area of the pipette station 6, adiametrically opposite rinsing station 18 equipped with one or severalrinsing bowls, and two sampling areas 19, 20 placed symmetrically withrespect to the axis passing through the pipette area 6 and the rinsingarea 18.

The sampling areas 19, 20 are situated in the path of the receptaclesRE₁, RE₂ borne by two respective carousels CR₁, CR₂ moving in rotationaround two vertical spindles 21, 22 and controlled by two motorscontrolled by the processor P.

One of these carrousels CR₁ is used to contain the receptacles RE₁ ofthe blood samples to be analysed, whereas the other carrousel CR₂contains receptacles RE₂ allocated to the various reactive agents ableto be used as part of the analyses it is desired to carry out.

Of course, the processor P is programmed so as to control pipettesequences appropriate to the nature of the analyses to be conducted andpossibly successively comprising:

-   -   a prior rinsing of the pipette 15,    -   the taking of a sample dose contained in one of the receptacles        RE₁ of the carrousel CR₁,    -   the injection of this dose into a bowl C situated in the pipette        station 6,    -   the rinsing of the pipette 15,    -   the taking of a reactive agent dose contained in one of the        receptacles RE₂ of the carrousel CR₂,    -   the injection of this reactive agent dose into the bowl C,    -   the identification of the blood samples to be analysed and that        of the reactive agents being carried out automatically by means        of a bar code reader 23 able to carry out a reading of the bar        codes present on the receptacles RE₁, RE₂ borne by the        carrousels CR₁, CR₂.

In this example, for these readings, the sole bar code reader 23 ismounted at the extremity of an arm 24 pivoting around a vertical spindle25 so as to be able to occupy three positions, namely:

-   -   a position P₁ for reading the bar codes of the receptacles RE₁        of the carrousel CR₁,    -   a position P₂ for reading the bar codes of the receptacles RE₂        of the carrousel CR₂, and    -   a position P₃ for reading the receptacles placed by the operator        in a reading station with a view, for example, of entering the        information exploited by the processor within the context of        functioning of the device.        The measuring station 7 here comprises three successive        measuring positions, each comprising (FIG. 4) a pair of coaxial        electromagnets E₁, E′₁-E₂, E′₂-E₃, E′₃ situated on both sides of        the film (3) at the right of the lateral faces of the bowls C.

The station 7 also comprises:

-   -   an infrared light source 26 situated above the bowl,    -   a load transfer detector bar (DTC) 27 situated below the bowls C        borne by the film onto which the image of the ball illuminated        by the light source is projected.

The use of several measuring positions on the path of the film has theadvantage of permitting greater flexibility of operation.

It is to be noted that the light source, which is secured to the rail 5,moreover ensures support via the top of the bowls/film unit so as toavoid the coming out of the rail.

The electromagnets E₁, E′₁-E₂, E′₂-E₃, E′₃ are excited by a powercircuit PR controlled by the processor P so as to generate a magneticpulse field able to drive the ball BE along an alternative movement atthe bottom of the bowl C.

The camera 27 is coupled to the processor P which carries out a realtime analysis of the image by means of a suitable software so as tomeasure the amplitude of the oscillations of the ball BE and determinethe critical instant when this amplitude falls below a specificthreshold (for example 50% of the initial amplitude).

Of course, the processor P counts the time between the moment when thereactive agent has been injected into the bowl C and this criticalinstant so as to deduce from this a coagulation time.

The movements of the film are synchronised with the operating times ofeach of the stations of the device and in particular with the magneticfiled pulses generated by the coils.

The pipette station could also be situated at the same location as themeasuring station.

Of course, the invention is not limited to the embodiment previouslydescribed.

Thus, for example, each infrared source/camera unit could have a fieldcomprising several bowls each excited by a pair of separateelectromagnets so as to follow the bowl over a forward movement ofseveral steps with a processor P programmed to simultaneously detect themovements of the balls of different bowls.

1. Device for automatically analysing a liquid sample, this devicecomprising a series of bowls for sole usage and each comprising abottom, one upper face opposite the bottom having one opening and twoopposing shoulders extending on both sides of the bowl approximatelyinside the plane of the opening, the bowls being placed side by side andjoined to each other by a flexible film secured to said shoulders andcovering at least partially the openings of said bowls, wherein the filmhas a series of orifices situated respectively at the right of theopenings of said bowls which have been dimensioned so as to allow the nocontact engaging of the injection and/or sampling means.
 2. Deviceaccording to claim 1, comprising an optical detection stationintroducing a light source illuminating the upper face of the bowl, andan opto-electronic detector placed below the bottom.
 3. Device accordingto claim 1, wherein the film is made of a diffusing material for thelight rendering the luminous beam more homogeneous.
 4. Device accordingto claim 1, wherein the dimensions of the orifice are determinedaccording to the dimensions of the pipette, its position and thesought-after homogeneity of the intensity of the luminous beamstraversing a predetermined working volume of the bowl.
 5. Deviceaccording to claim 1, wherein the bottom of the bowls constitutes therolling path of a ball driven by an external magnetic field.
 6. Deviceaccording to claim 4, wherein said orifice has the shape of an openingcentered partially on the rolling path of the ball and whose width isslightly smaller than the diameter of the ball.
 7. Device according toclaim 1, wherein the material constituting the film possesses liquidabsorption properties.
 8. Device according to claim 1, wherein theseries of bowls follow a path passing successively through a pipettestation, a detection station and a station for cutting the analysedbowls.
 9. Device according to claim 1, wherein said analysed bowls arecollected in a single container.
 10. Device according to claim 1,wherein said shoulders have a shape enabling them to gear between thenotches of a drive belt.
 11. Device according to claim 10, wherein saidnotches have an involute to a circle profile corresponding to a normaltooth-shaped rack.
 12. Device according to claim 10, wherein saidshoulders have the shape of an isosceles trapezium whose large base isintegral with the bowl.
 13. Device according to claim 12, wherein thelateral borders of the film have in the interval of the shoulders ofsuccessive bowls trapezoidal cuts whose oblique edges extend to theright of the oblique edges of the shoulders.
 14. Device according toclaim 2, wherein the light source of said detection station is aninfrared light source and the opto-electronic detector is a camera. 15.Device according to claim 2, wherein the support of the light sourcesecured to the rail supports the bowls/film unit via the top.
 16. Deviceaccording to claim 5, wherein the external magnetic field is generatedby electromagnetic means placed lateral with respect to the series ofbowls at the right of their lateral faces.